Adrenergic antagonist drug

 

Mechanism of action

Opioids exert their major effects by interacting with opioid receptors in the CNS and in other anatomic structures, such as the GI tract and the urinary bladder. Opioids cause hyperpolarization of nerve cells, inhibition of nerve firing, and presynaptic inhibition of transmitter release. Morphine acts at κ receptors in laminae I and II of the dorsal horn of the spinal cord, and it decreases the release of substance P, which modulates pain perception in the spinal cord. Morphine also appears to inhibit the release of many excitatory transmitters from nerve terminals carrying nociceptive (painful) stimuli. 

Actions 

• CNS :

 Analgesia, sedation, euphoria due to stimulation of μ receptors.

• Respiration :

Morphine sulfate cause respiratory depression due to inhibition of respiratory center in the brain ( by reduction of sensitivity of neurons of respiratory center to carbon dioxide).

• Emesis :

Morphine sulfate induce emesis by stimulation of chemoreceptor trigger zone (CTZ) in the brain.

• Cough suppression :

Antitussive effects does not related to the receptors involved in analgesic and respiratory depressant properties of morphine sulfate .

• Cardiovascular :

 Morphine sulfate cause hypotension due increased histamine release from mast cells (vasodilatory effects) and cause bradycardia due to stimulation of vagal center in the brain.

• Pupil :

Morphine sulfate cause miosis called pin point pupil (PPP) due stimulation of μ & K receptors in the occulomotor nerve.

• GIT :

Morphine sulfate cause constipation due to decreased intestinal peristalsis by stimulation of μ receptors in the intestine.

• Endocrine :

Morphine sulfate increase the release of Antidiuretic hormone (ADH) which leads to urinary retention, increase the release of growth hormone (GH), decrease the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) & adrenocorticotropic hormone (ACTH).

• Labor :

Morphine sulfate may prolong the second stage of labor by transiently decreasing the strength, duration, and frequency of uterine contractions.

 

Therapeutic uses

• Analgesia :

 For severe pain, eg : myocardial infarction, cancer, fracture & postoperative pain.

• Treatment of diarrhea.

•  Relief of cough :

Although morphine sulfate can be used for cough suppression, but codeine & dextromethorphan are more widely used for this purpose.

• Treatment of pulmonary edema :

Intravenous (IV) morphine dramatically relieves dyspnea caused by pulmonary edema associated with left ventricular failure, possibly by its vasodilatory effect.

• Used as preanesthetic medication.

Pharmacokinetics 

• Administration :

Because significant  first pass effect of morphine, intramuscular (IM), intravenous (IV) & subcutaneous (SC) are more widely used.Absorption of morphine from the GI tract is slow and erratic, so oral morphine is more commonly administered in the extended release dosageforms to provide consistent plasma levels.

• Distribution :

Morphine sulfate rapidly enters all tissues, including the fetuses of pregnant women, and should not be used for analgesia during labor.Only small percentage of morphine enter blood brain barrier (BBB) because morphine is the least lipophilic opioid. 

• Fate :

Morphine sulfate is conjugated in the liver with glucuronic acid.Morphine 6 conjugates are very potent analgesics, whereas morphine 3 conjugates have been found  to be inactive ( have no opioid activity).

Adverse effects

Respiratory depression, vomiting, constipation, urinary retention, miosis, hypotension & physical dependence.

 

Morphine sulfate during pregnancy and labor

Morphine sulfate is contraindicated in pregnancy because it delay labor & may cause respiratory depression of the fetus.

Contraindications

 • Bronchial asthma (because morphine cause respiratory depression).

• Head injury ( because morphine increase intracranial pressure).

• Paralytic ileus ( because morphine decrease intestinal motility).

• Benign prostatic hyperplasia (because of urinary retention caused by morphine).

• Pregnancy & labor ( because morphine delay labor & may cause respiratory depression of the fetus).